Autoimmune regulator initiates the expression of promiscuous genes in thymic epithelial cells

The expression of peripheral antigens in the thymus, known as promiscuous gene expression, has been implicated in T cell tolerance and autoimmunity. Here we identified thymic epithelial cells (TECs) as the main cell type that expresses a diverse range of tissue-restricted antigens (TRAs). The TECs of a common autoimmune (non-obese diabetic [NOD]) mouse model express much lower levels of an autoimmune regulator (Aire) and TRAs than normal (Balb/c) TECs. Transfection of an Aire plasmid led to increased levels of TRA expression in cultured TECs from Balb/c and NOD mice; an increase that was enhanced by the presence of thymocytes. These data show that Aire initiates promiscuous gene expression in TECs, and that this function might be under thymocyte control.